The primary treatment for Gastroenteropancreatic Neuroendocrine tumors (GEP-NETS), such as carcinoid tumors, is surgery with curative intent. However, in many patients this is often impossible and alternatives such as external beam radiation or chemotherapy are sub-optimal because these well-differentiated tumors are relatively unresponsive. Most of these tumors express somatostatin receptors, especially sub-type 2, in high abundance, which very rapidly bind and internalize targeted peptides. Other cancers, such as ovarian cancer, also exhibit somatostatin receptors.
Somatostatin analogues, such as lanreotide and octreotide, as well as octreotate, have been tested as a means to deliver a radioisotope to the cancerous tissue. Generally, the somatostatin peptide analogues are coupled with a complexing agent such as DOTA (1,4,7,10-tetra-azacyclododecane-N,N′,N″,N′″-tetraacetic acid). Other complexing moieties are disclosed for example in PCT/EP01/08824. Both Yttrium-90 and Lutetium-177 have been used to deliver a tumoricidal radiation dose. Lutetium is a medium energy beta emitter with a maximum tissue penetration of 1.6 mm and a physical half life of 6.7 days. It also emits medium and low energy gamma radiation. But the gamma radiation provides very poor resolution for imaging purposes. Gallium-68 is a positron emitter and has been used for imaging, but has limited therapeutic benefit. However, none of these radioisotopes are optimal from a therapeutic perspective.
Depending on the delivery system and mode of elimination from the body, some beta emitters can adversely affect the kidneys and other organs, and some alpha emitters create systemic problems such as gastrointestinal and pulmonary adverse events. Further, many alpha emitters cannot be imaged.